Late effects of high-dose methotrexate treatment in childhood cancer survivors-a systematic review

BACKGROUND: High-dose methotrexate (HD-MTX) is used in the treatment of different childhood cancers, including leukemia, the most common cancer type and is commonly defined as an intravenous dose of at least 1 g/m$^{2}$ body surface area per application. A systematic review on late effects on different organs due to HD-MTX is lacking. METHOD: We conducted a systematic literature search in PubMed, including studies published in English or German between 1985 and 2020. The population of each study had to consist of at least 75% childhood cancer survivors (CCSs) who had completed the cancer treatment at least twelve months before late effects were assessed and who had received HD-MTX. The literature search was not restricted to specific cancer diagnosis or organ systems at risk for late effects. We excluded case reports, case series, commentaries, editorial letters, poster abstracts, narrative reviews and studies only reporting prevalence of late effects. We followed PRISMA guidelines, assessed the quality of the eligible studies according to GRADE criteria and registered the protocol on PROSPERO (ID: CRD42020212262). RESULTS: We included 15 out of 1731 identified studies. Most studies included CCSs diagnosed with acute lymphoblastic leukemia (n = 12). The included studies investigated late effects of HD-MTX on central nervous system (n = 10), renal (n = 2) and bone health (n = 3). Nine studies showed adverse outcomes in neuropsychological testing in exposed compared to non-exposed CCSs, healthy controls or reference values. No study revealed lower bone density or worse renal function in exposed CCSs. As a limitation, the overall quality of the studies per organ system was low to very low, mainly due to selection bias, missing adjustment for important confounders and low precision. CONCLUSIONS: CCSs treated with HD-MTX might benefit from neuropsychological testing, to intervene early in case of abnormal results. Methodological shortcomings and heterogeneity of the tests used made it impossible to determine the most appropriate test. Based on the few studies on renal function and bone health, regular screening for dysfunction seems not to be justified. Only screening for neurocognitive late effects is warranted in CCSs treated with HD-MTX

Professionalisation in nursing : the Swiss case

In this study, the professionalisation of nursing in Switzerland is being investigated with the help of the theoretical approaches of the sociology of professions. These approaches - demand approach and supply approach - represent two opposing lines of argumentation. In the demand approach, the status of being a profession (monopolised autonomy by state licence, social standing) is ascribed to successful political strategies of the professional group. In the supply approach, the professions are seen as institutions which can only be explained in their relationship to the state. Thus, in one line of thought, the constitution of the professions is viewed as a process parallel to the modernisation of the state. Another line of thought understands the professions also as bearers of uncertainty of both individuals and collectives. In the course of global neo-liberal politics, the ethic aspect of this approach has been condensed into the soul of the professions - as an antagonist to the soullessness of state and market. Since the 1950s, leading nurses in teaching and practice in Switzerland have been active to create a new position for professional nursing. Their main concern is to develop autonomous, specific concepts in addition to the traditionally dominant concepts of medicine. As a result, a professional project evolved which aims to gain a state monopoly for professional nursing. The study shows that the demand approach can only explain single aspects and short historic phases in the development of the profession. In each development phase, state and market have created the prevailing conditions of nursing like, so to speak, a mould. This becomes manifest in each phase depending on the federal structures of the state. This corresponds to the supply approach of the sociology of the professions. Nursing has not reached the goal of state licensure. However, if the profession thanks to its professional soul independently stands up for its patients, it fulfils the role typical of professions in this theoretic approach. This soul was present in the nursing profession from its very beginning

The importance of information on relatives for the prediction of genomic breeding values and the implications for the makeup of reference data sets in livestock breeding schemes.

<p>Abstract</p> <p>Background</p> <p>The theory of genomic selection is based on the prediction of the effects of genetic markers in linkage disequilibrium with quantitative trait loci. However, genomic selection also relies on relationships between individuals to accurately predict genetic value. This study aimed to examine the importance of information on relatives versus that of unrelated or more distantly related individuals on the estimation of genomic breeding values.</p> <p>Methods</p> <p>Simulated and real data were used to examine the effects of various degrees of relationship on the accuracy of genomic selection. Genomic Best Linear Unbiased Prediction (gBLUP) was compared to two pedigree based BLUP methods, one with a shallow one generation pedigree and the other with a deep ten generation pedigree. The accuracy of estimated breeding values for different groups of selection candidates that had varying degrees of relationships to a reference data set of 1750 animals was investigated.</p> <p>Results</p> <p>The gBLUP method predicted breeding values more accurately than BLUP. The most accurate breeding values were estimated using gBLUP for closely related animals. Similarly, the pedigree based BLUP methods were also accurate for closely related animals, however when the pedigree based BLUP methods were used to predict unrelated animals, the accuracy was close to zero. In contrast, gBLUP breeding values, for animals that had no pedigree relationship with animals in the reference data set, allowed substantial accuracy.</p> <p>Conclusions</p> <p>An animal's relationship to the reference data set is an important factor for the accuracy of genomic predictions. Animals that share a close relationship to the reference data set had the highest accuracy from genomic predictions. However a baseline accuracy that is driven by the reference data set size and the overall population effective population size enables gBLUP to estimate a breeding value for unrelated animals within a population (breed), using information previously ignored by pedigree based BLUP methods.</p

Comparing linkage and association analyses in sheep points to a better way of doing GWAS

Genome wide association studies (GWAS) have largely succeeded family-based linkage studies in livestock and human populations as the preferred method to map loci for complex or quantitative traits. However, the type of results produced by the two analyses contrast sharply due to differences in linkage disequilibrium (LD) imposed by the design of studies. In this paper, we demonstrate that association and linkage studies are in agreement provided that (i) the effects from both studies are estimated appropriately as random effects, (ii) all markers are fitted simultaneously and (iii) appropriate adjustments are made for the differences in LD between the study designs. We demonstrate with real data that linkage results can be predicted by the sum of association effects. Our association study captured most of the linkage information because we could predict the linkage results with moderate accuracy. We suggest that the ability of common single nucleotide polymorphism (SNP) to capture the genetic variance in a population will depend on the effective population size of the study organism. The results provide further evidence for many loci of small effect underlying complex traits. The analysis suggests a more informed method for GWAS is to fit statistical models where all SNPs are analysed simultaneously and as random effects

Consultando os Livros Sibilinos: a expiação de prodígios na República Romana

A religião romana estava profundamente interligada com vários aspectos da vida dos habitantes de Roma, principalmente na política e nas interações sociais. No século III antes da era comum, a República Romana expandiu seus territórios pela Península Itálica, se tornando uma grande potência econômica e militar na região. Essa mudança, trouxe um grande impacto para Roma na esfera religiosa também, com divindades estrangeiras ganhando um local de culto dentro da cidade de Roma. O presente artigo procura analisar uma maneira específica na qual os antigos romanos estabeleceram novos templos e cultos para deuses e deusas estrangeiras, através da consulta dos Livros Sibilinos, uma ação realizada para expiar prodígios que foram reportados

Professionalisation in nursing : the Swiss case

In this study, the professionalisation of nursing in Switzerland is being investigated with the help of the theoretical approaches of the sociology of professions. These approaches - demand approach and supply approach - represent two opposing lines of argumentation. In the demand approach, the status of being a profession (monopolised autonomy by state licence, social standing) is ascribed to successful political strategies of the professional group. In the supply approach, the professions are seen as institutions which can only be explained in their relationship to the state. Thus, in one line of thought, the constitution of the professions is viewed as a process parallel to the modernisation of the state. Another line of thought understands the professions also as bearers of uncertainty of both individuals and collectives. In the course of global neo-liberal politics, the ethic aspect of this approach has been condensed into the soul of the professions - as an antagonist to the soullessness of state and market. Since the 1950s, leading nurses in teaching and practice in Switzerland have been active to create a new position for professional nursing. Their main concern is to develop autonomous, specific concepts in addition to the traditionally dominant concepts of medicine. As a result, a professional project evolved which aims to gain a state monopoly for professional nursing. The study shows that the demand approach can only explain single aspects and short historic phases in the development of the profession. In each development phase, state and market have created the prevailing conditions of nursing like, so to speak, a mould. This becomes manifest in each phase depending on the federal structures of the state. This corresponds to the supply approach of the sociology of the professions. Nursing has not reached the goal of state licensure. However, if the profession thanks to its professional soul independently stands up for its patients, it fulfils the role typical of professions in this theoretic approach. This soul was present in the nursing profession from its very beginning

Uncertainty-driven refinement of tumor-core segmentation using 3D-to-2D networks with label uncertainty

The BraTS dataset contains a mixture of high-grade and low-grade gliomas, which have a rather different appearance: previous studies have shown that performance can be improved by separated training on low-grade gliomas (LGGs) and high-grade gliomas (HGGs), but in practice this information is not available at test time to decide which model to use. By contrast with HGGs, LGGs often present no sharp boundary between the tumor core and the surrounding edema, but rather a gradual reduction of tumor-cell density. Utilizing our 3D-to-2D fully convolutional architecture, DeepSCAN, which ranked highly in the 2019 BraTS challenge and was trained using an uncertainty-aware loss, we separate cases into those with a confidently segmented core, and those with a vaguely segmented or missing core. Since by assumption every tumor has a core, we reduce the threshold for classification of core tissue in those cases where the core, as segmented by the classifier, is vaguely defined or missing. We then predict survival of high-grade glioma patients using a fusion of linear regression and random forest classification, based on age, number of distinct tumor components, and number of distinct tumor cores. We present results on the validation dataset of the Multimodal Brain Tumor Segmentation Challenge 2020 (segmentation and uncertainty challenge), and on the testing set, where the method achieved 4th place in Segmentation, 1st place in uncertainty estimation, and 1st place in Survival prediction.Comment: Presented (virtually) in the MICCAI Brainles workshop 2020. Accepted for publication in Brainles proceeding

Accuracy of estimated genomic breeding values for wool and meat traits in a multi-breed sheep population

Estimated breeding values for the selection of more profitable sheep for the sheep meat and wool industries are currently based on pedigree and phenotypic records. With the advent of a medium-density DNA marker array, which genotypes ∼50000 ovine single nucleotide polymorphisms, a third source of information has become available. The aim of this paper was to determine whether this genomic information can be used to predict estimated breeding values for wool and meat traits. The effects of all single nucleotide polymorphism markers in a multi-breed sheep reference population of 7180 individuals with phenotypic records were estimated to derive prediction equations for genomic estimated breeding values (GEBV) for greasy fleece weight, fibre diameter, staple strength, breech wrinkle score, weight at ultrasound scanning, scanned eye muscle depth and scanned fat depth. Five hundred and forty industry sires with very accurate Australian sheep breeding values were used as a validation population and the accuracies of GEBV were assessed according to correlations between GEBV and Australian sheep breeding values . The accuracies of GEBV ranged from 0.15 to 0.79 for wool traits in Merino sheep and from 0.07 to 0.57 for meat traits in all breeds studied. Merino industry sires tended to have more accurate GEBV than terminal and maternal breeds because the reference population consisted mainly of Merino haplotypes. The lower accuracy for terminal and maternal breeds suggests that the density of genetic markers used was not high enough for accurate across-breed prediction of marker effects. Our results indicate that an increase in the size of the reference population will increase the accuracy of GEBV

Genetic Contribution of Emmer Wheat (Triticum dicoccon Schrank) to Heat Tolerance of Bread Wheat

Rising global temperatures cause substantial yield losses in many wheat growing environments. Emmer wheat (Triticum dicoccon Schrank), one of the first wheat species domesticated, carries significant variation for tolerance to abiotic stresses. This study identified new genetic variability for high-temperature tolerance in hexaploid progeny derived from crosses with emmer wheat. Eight hexaploid and 11 tetraploid parents were recombined in 43 backcross combinations using the hexaploid as the recurrent parent. A total of 537 emmer-based hexaploid lines were developed by producing approximately 10 doubled haploids on hexaploid like BC1F1 progeny and subsequent selection for hexaploid morphology. These materials and 17 commercial cultivars and hexaploid recurrent parents were evaluated under two times of sowing in the field, in 2014–2016. The materials were genotyped using a 90K SNP platform and these data were used to estimate the contribution of emmer wheat to the progeny. Significant phenotypic and genetic variation for key agronomical traits including grain yield, TKW and screenings was observed. Many of the emmer derived lines showed improved performance under heat stress (delayed sowing) compared with parents and commercial cultivars. Emmer derived lines were the highest yielding material in both sowing dates. The emmer wheat parent contributed between 1 and 44% of the genome of the derived lines. Emmer derived lines with superior kernel weight and yield generally had a greater genetic contribution from the emmer parent compared to those with lower trait values. The study showed that new genetic variation for key traits such as yield, kernel weight and screenings can be introduced to hexaploid wheat from emmer wheat. These genetic resources should be explored more systematically to stabilize grain yield and quality in a changing climate

Endodontic Obturation: A Volumetric Analysis Using 3D Imaging Technology

poster abstractAbstract: A Root Canal (RC) obturation that fully occupies that prepared canal space contributes to treatment success. Invasive methods that involve sectioning of treated teeth have been used evaluate the quality of RC obturation. The aim of this study was to measure the amount of filling material in RC treated teeth using imaging methods: Cone Beam Computed tomography (CBCT) and 3D volumetric imaging software. These methods will be applied in an analysis of both Warm Vertical (WV) and Cold Lateral (CL) obturation methods. This noninvasive approach may be a preliminary step for future in vivo research. A noninvasive 3D imaging method was able to measure volume of RC fillings. Canals filled using WV contained a greater percentage of empty space than canals filled using the CL method in this study. This method could prove to be an efficient, cost effective tool for evaluating obturation material